Tuberculosis continues to disproportionately affect many Indigenous populations in the USA, Canada, and Greenland. We aimed to investigate whether population-based tuberculosis-specific interventions or changes in general health and socioeconomic indicators, or a combination of these factors, were associated with changes in tuberculosis incidence in these Indigenous populations.

Methods

For this population-based study we examined annual tuberculosis notification rates between 1960 and 2014 in six Indigenous populations of the USA, Canada, and Greenland (Inuit [Greenland], American Indian and Alaska Native [Alaska, USA], First Nations [Alberta, Canada], Cree of Eeyou Istchee [Quebec, Canada], Inuit of Nunavik [Quebec, Canada], and Inuit of Nunavut [Canada]), as well as the general population of Canada.

We used mixed-model linear regression to estimate the association of these rates with population-wide interventions of bacillus Calmette-Guérin (BCG) vaccination of infants, radiographic screening, or testing and treatment for latent tuberculosis infection (LTBI), and with other health and socioeconomic indicators including life expectancy, infant mortality, diabetes, obesity, smoking, alcohol use, crowded housing, employment, education, and health expenditures.

Findings

Tuberculosis notification rates declined rapidly in all six Indigenous populations between 1960 and 1980, with continued decline in Indigenous populations in Alberta, Alaska, and Eeyou Istchee thereafter but recrudescence in Inuit populations of Nunavut, Nunavik, and Greenland.

Annual percentage reductions in tuberculosis incidence were significantly associated with two tuberculosis control interventions, relative to no intervention, and after adjustment for infant mortality and smoking: BCG vaccination (–11%, 95% CI −6 to −17) and LTBI screening and treatment (–10%, −3 to −18). Adjusted associations were not significant for chest radiographic screening (–1%, 95% CI −7 to 5).

Declining tuberculosis notification rates were significantly associated with increased life expectancy (–37·8 [95% CI −41·7 to −33·9] fewer cases per 100 000 for each 1-year increase) and decreased infant mortality (–9·0 [–9·5 to −8·6] fewer cases per 100 000 for each death averted per 1000 livebirths) in all six Indigenous populations, but no significant associations were observed for other health and socioeconomic indicators examined.

Interpretation

Population-based BCG vaccination of infants and LTBI screening and treatment were associated with significant decreases in tuberculosis notification rates in these Indigenous populations. These interventions should be reinforced in populations still affected by tuberculosis, while also addressing the persistent health and socioeconomic disparities.

January 29, 2018

An emergency tuberculosis clinic is taking over the community hall in Qikiqtarjuaq, Nunavut, on Feb. 5. The mobile clinic will run for seven to 10 weeks and will screen every person in the community of 600 for the disease.

Qikiqtarjuaq, a hamlet on the eastern coast of Baffin Island, has the highest rate of tuberculosis in the territory, with almost 10 per cent of the population infected. Dr. Kim Barker, Nunavut's chief medical officer of health, says 17 of the territory's 25 communities have cases of tuberculosis.

"It's now hit a point where if you just take one patient and screen all their contacts you might as well have screened the entire community," Barker said.

Symptoms can include a fever, sweating, loss of appetite, unintentional weight loss, and coughing up phlegm or even blood. Tuberculosis can lead to death if left untreated.

Repeatable strategy

If this new approach to treatment goes well, the clinic will be packed up and rolled out in the remaining 16 communities.

The clinic will cost nearly $1 million to host in Qikiqtarjuaq, but the equipment, provided by the Public Health Agency of Canada, is mobile and will be reused in other communities. The government of Nunavut applied and received most of the project funding from the federal government.

Barker said the mayor of Qikiqtarjuaq has been helping the Health Department identify households that can be brought in all at once for screening. The Department of Education has provided the team with class lists so no children are missed.

Around 12 medical personnel will be on the ground for the clinic's duration, including respiratory therapists, X-ray technicians and an epidemiologist.

Technicians are already in town setting up computers and X-ray equipment. Pillows, blankets, blood pressure machines, crash carts, privacy screens, and contagion-proof testing cubicles have also been shipped up. This mobile clinic is what the Public Health Agency of Canada sends out in emergency situations, as they did during the 2016 Fort McMurray wildfires.

The team will check back in a few months to ensure those residents put on drug treatments have stuck with the routine and beaten the disease.

The project will be reviewed by two tuberculosis experts in March and they will follow up annually for the next four years to make sure the program stays on track.

Number of active TB cases doubles in 2017

In 2017, Nunavut had 101 cases of active tuberculosis, making it the highest year on record since the territory was formed in 1999. In 2016, Nunavut had just 53 cases.

The most commonly reported resistant bacteria were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae, followed by Salmonella spp. The system does not include data on resistance of Mycobacterium tuberculosis, which causes tuberculosis (TB), as WHO has been tracking it since 1994 and providing annual updates in the Global tuberculosis report.

Among patients with suspected bloodstream infection, the proportion that had bacteria resistant to at least one of the most commonly used antibiotics ranged tremendously between different countries – from zero to 82%. Resistance to penicillin – the medicine used for decades worldwide to treat pneumonia – ranged from zero to 51% among reporting countries. And between 8% to 65% of E. coli associated with urinary tract infections presented resistance to ciprofloxacin, an antibiotic commonly used to treat this condition.

“Some of the world’s most common – and potentially most dangerous – infections are proving drug-resistant,” adds Sprenger. “And most worrying of all, pathogens don’t respect national borders. That’s why WHO is encouraging all countries to set up good surveillance systems for detecting drug resistance that can provide data to this global system.”

To date, 52 countries (25 high-income, 20 middle-income and 7 low-income countries) are enrolled in WHO’s Global Antimicrobial Surveillance System. For the first report, 40 countries provided information about their national surveillance systems and 22 countries also provided data on levels of antibiotic resistance.

The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.

Methods

On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.

Findings

Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.

Interpretation

Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.

December 26, 2017

After scampering about a sleek glass and aluminium cage, a rat named Riziwan has made a crucial discovery.

In just minutes, Riziwan has positively identified 13 people who may have tuberculosis. The discovery is potentially life-saving news for those whose sputum samples were marked as clear by their local health clinics. But it’s all in a day’s – or rather 15 minutes’ – work for Riziwan and the other giant African pouched rats that work at Belgian organisation Apopo’s TB centre in Morogoro, Tanzania.

Riziwan, now almost a year old, has been trained – almost since birth – to pick up the smell of the disease, which is notoriously difficult to detect.

To carry out his work, Riziwan is placed in a large cage. Into its base, technicians insert a metal bar holding 10 dishes of human sputum, sent to Apopo by a TB clinic. All samples have been heat-treated so there is no risk of infection to either rats or humans. One by one, metal grates in the bottom of the cage are opened to allow Riziwan to sniff each petri dish.

There is silence among the technicians as Riziwan examines the samples. He moves on quickly from slots one and two, but at the third he pauses and scratches the metal bottom of the cage, indicating that he smells the disease.

At the seventh hole he scratches again, and again at the eighth. This time Harumi Ramadhani, the training supervisor, presses a clicker, meaning Riziwan has correctly identified a control sample from one of the clinics. It earns him a reward of mashed banana, avocado and rat pellets.

In all, Riziwan checks 100 samples. His work done for the day, he is returned to a large open-air playpen. The cage is cleaned and a second rat – a female named Pink – is brought in to test his findings.

“No person will be treated only on the statement of a rat,” says Lena Fiebig, head of the TB programme at Apopo. “The rats at this moment are not approved as a standalone diagnostic tool. We’ll then use a recognised method, and this is mostly concentrated microscopy, where a lab technician will re-check these samples. But the rats have already contributed tremendously to narrowing down the focus, so it’s not a team of 10 lab technicians who need a week to re-check.”

On average, Apopo rats find an additional 40% of TB cases on top of those discovered by clinics. Since they started work 10 years ago, they have screened nearly half a million samples and detected more than 12,200 missed cases. They can get through 100 samples in 10 to 20 minutes: a human with a microscope takes four days to test the same number.

The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.

Methods

We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria.

Findings

We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier.

Interpretation

Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori.

An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories.

Methods

We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool.

We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes.

Findings

Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million).

Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (−4·1% [−5·0 to −3·4]) than in incidence (−1·6% [−1·9 to −1·2]) and prevalence (−0·7% [−1·0 to −0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence.

Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3–13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8–14·8), and smoking accounted for 7·8% (3·8–12·0).

Interpretation

Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis.

November 25, 2017

Unless control efforts are stepped up, tuberculosis will kill 28 million people between 2015 and 2030, and cost the global economy almost US$1 trillion, according to a new report.

The investigators based their estimates on a “business as usual” scenario, in which progress continues on its present course. They noted that tuberculosis cost the world economy $616 billion from 2000–15, and that economic losses in several countries in Africa and southeast Asia exceeded 1% of gross domestic product (GDP).

The following 15 years are likely to be even more damaging. India is projected to lose $252·7 billion, and Lesotho and Mozambique face losing more than 3% of GDP. The authors predicted that the overall cost of the disease would be $984 billion, almost a third of which would fall on Africa.

The Global TB Caucus, a network of 2300 parliamentarians in 130 countries, commissioned the report. The Caucus is chaired by UK member of parliament Nick Herbert. He points out that 2015–30 represents the duration of the sustainable development goals (SDGs).

“The world has set an SDG that says we can beat tuberculosis in 15 years; on the current trajectory, that is not going to happen for 150 years, and we will see another 28 million deaths by 2030”, Herbert told The Lancet Respiratory Medicine. “That is not a great advertisement for the SDGs.”

He added that the costs of taking concerted action are dwarfed by the costs of not doing so. The 2016–20 Global Plan to End TB calls for an investment of $65 billion.

The Caucus report was launched in advance of a ministerial conference on tuberculosis in Moscow, Russia. The conference was opened by President Vladimir Putin. 75 ministers attended, as well as delegations from 125 nations.

“It was by far the largest event in the history of the tuberculosis response”, said Mario Raviglione, who will retire as director of WHO's Global TB Programme on Nov 30. “We have created the momentum that we need to proceed to next year's UN General Assembly meeting on TB”.

A declaration issued at the Moscow conference will help inform discussions at the general assembly. “Tuberculosis has not had the necessary political attention, and at last that is changing”, concluded Herbert.

The burden of MDR TB in children in the EU/EEA appears low and stable over time. Laboratory confirmation of paediatric TB remains a challenge in EU/EEA and may lead to an underestimation of the real burden of MDR TB among children. Improvements in the laboratory diagnosis of paediatric TB are needed for early detection and adequate treatment of MDR TB. Children previously treated for TB and children of foreign origin may need to be given higher attention regarding MDR TB.

ECDC and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) have systematically retrieved and assessed evidence on active case findings for blood-borne viruses like HIV, hepatitis B and C, sexually transmitted infections as well as tuberculosis in prison settings in the EU/EEA.

Compared with the general public, people in prison have a higher prevalence of infection with HIV, hepatitis B, hepatitis C, syphilis, gonorrhoea, chlamydia and tuberculosis. Such increased prevalence of diseases among people in prisons is recognised as a major risk for the health of both people living and working in prison settings and for the general population, as the vast majority of people in prisons return to their communities after less than 24 months of incarceration.

According to the principle of equivalence of care, people in prison should enjoy an equivalent standard of care as in the community. Yet, their health needs tend to be greater. Incarceration may thus represent a unique opportunity to make adequate healthcare services available to people and target groups that usually are hard to reach.

Active case finding to promote early diagnosis is a key measure to prevent onward transmission of communicable diseases and allow entry into care to individuals in need. As its broader implementation may be particularly relevant for prison settings, the available evidence was assessed in a systematic literature review, performed by ECDC and EMCDDA.

Despite some limitations, the findings provide a valid argument to strengthen case finding initiatives in prison settings. They also show that, in such settings, the way testing is organized and offered to people in detention, influences the uptake of tests for communicable diseases.

For example, the available evidence suggests that the active offer of tests by health care provider yields a higher uptake compared with people in prison having to ask for test themselves. However, due to lack of research, current evidence does not provide a clear indication on the most effective timing and optimal testing modalities for these diseases in prison settings.

This systematic review highlights important knowledge gaps. More operational research is needed to assess the effectiveness of interventions to increase the offer and uptake of testing in prison settings.